RX871024 INDUCES CA2-SENSITIVE STORES IN MOUSE PANCREATIC BETA-CELLS(MOBILIZATION FROM THAPSIGARGIN)

The effects of RX871024, a compound with an imidazoline structure, on cytoplasmic-free Ca2+ concentration ([Ca2+](i)) in mouse pancreatic be ta-cells were studied. RX871024 modulates [Ca2+](i) by at least two me chanisms. One mechanism involves closure of ATP-regulated K+ channels, resulting in membrane depolarization, opening of voltage-gated L-type Ca2+ channels, and a subsequent increase in [Ca2+](i). Another mechan ism, reported here for the first time, deals with RX871024-induced mob ilization of Ca2+ from nonmitochondrial thapsigargin-sensitive intrace llular stores. Reduced glutathione, inhibitors of cytochrome P-450, an d monoaminooxidases A and B blocked this Ca2+ mobilization. It is conc luded that the mechanism of RX871024-induced Ca2+ mobilization from in tracellular stores involves changes in the oxidation/reduction state o f the pancreatic beta-cell and may be controlled by cytochrome P-450.